Effects of local MAO inhibition in the locus coeruleus on extracellular serotonin and 5-HIAA during exposure to sensory and cardiovascular stimuli

Previously, we have shown that in the presence of pargyline the release of serotonin (5-HT) in the locus coeruleus is modulated by various sensory sti muli and blood pressure fluctuations. The aim of the present study was to i nvestigate whether local inhibition of monoamine oxidase (MAO) influences b asal and stimulus-induced release of 5-HT in the locus coeruleus. For this purpose, the locus coeruleus was superfused in the absence and in the prese nce of the MAO inhibitor pargyline. Additionally, we examined whether the r elease of the 5-HT metabolite 5-hydroxy-indole acetic acid (5-HIAA) in the locus coeruleus is altered in response to stimuli. The locus coeruleus of t he conscious rat was superfused through a push-pull cannula with artificial cerebrospinal fluid (CSF). 5-HT and 5-HIAA were determined in the superfus ate. The basal release rate of 5-HT and the basal outflow of 5-HIAA averaged 2.0 fmol/min and 69 fmol/min, respectively. The basal release rate of 5-HT and the 5-HIAA outflow were tetrodotoxin (TTX)-sensitive. In the absence of pa rgyline, the sensory stimuli noise stress or tail pinch, applied for 10 min , increased 5-HT and 5-HIAA outflow by 50-70%. In contrast, an experimental ly induced rise in blood pressure for 10 min enhanced 5-HT release by 50%, but had no effect on 5-HIAA outflow. The release of 5-HT and/or 5-HIAA elic ited by sensory stimuli or a blood pressure rise was abolished by TTX. Addi tion of pargyline to the CSF enhanced 5-HT release fourfold and slightly de creased 5-HIAA outflow. These levels remained stable throughout the entire observation period of 8 h. In the presence of pargyline, 5-HT release elici ted by noise, tail pinch and increase in blood pressure was enhanced. It is concluded that superfusion with pargyline enhances 5-HT release and r educes 5-HIAA outflow in the locus coeruleus. Furthermore, the ability of s ensory stimuli and baroreceptor activation to enhance 5-HT release is prese rved during a prolonged pargyline-induced increase in extracellular 5-HT. S ince sensory stimuli enhanced, while baroreceptor activation did not influe nce 5-HIAA outflow, 5-HIAA is not a reliable index for short-term changes i n the activity of serotonergic neurons in the locus coeruleus.